Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma

J Cell Mol Med. 2014 Jun;18(6):947-61. doi: 10.1111/jcmm.12279. Epub 2014 Apr 8.


Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First-in-class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre-clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second-generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Recently, several of these new agents have been introduced into clinics including carfilzomib, marizomib and ixazomib. Further, new orally administered second-generation PI oprozomib is being investigated. This review provides an overview of main mechanisms of action of PIs in MM, focusing on the ongoing development and progress of novel anti-proteasome therapeutics.

Keywords: bortezomib; multiple myeloma; new-generation proteasome inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / enzymology
  • Proteasome Endopeptidase Complex / chemistry*
  • Proteasome Inhibitors / therapeutic use*


  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex